Tumor cells exhibit an enhanced ability to survive and proliferate in highly unfavorable environments. For example, tumor cells down-regulate many of the cellular pathways that prevent normal (i.e., non-cancerous) cells from dividing in a hostile environment. Tumor cells also inactivate apoptotic pathways that bring about the cell death of many normal tissues under adverse conditions. Tumor cells up-regulate pathways required to maintain active proliferation. For example, many tumor cells activate the cellular stress-response pathway that allows tumor cells to synthesize and maintain the protein machinery they need to continue proliferating. Activated stress response in tumors includes up-regulation of heat-shock proteins (Hsps), which are ATPase-directed molecular chaperones. In particular, Hsp90 is upregulated in many cancerous tissues. Hsp90 controls the balance between folding/maturation and proteasomal destruction of a restricted number of client proteins, some of which are involved in signal transduction and cell proliferation.
Members of the Inhibitor of Apoptosis (IAP) family of proteins are characterized by one or more Baculovirus IAP repeat domains. These proteins were first identified by their ability to enhance baculovirus propagation by preventing the defensive apoptosis of host insect cells. Survivin is a small 16.5 kDa mammalian member of the IAP family that is broadly expressed in embryonic and fetal organs, but becomes virtually undetectable in most terminally differentiated normal tissue. Survivin is highly expressed, however, in a variety of tumor tissues, and is thought to be involved in the mechanism by which many tumor cells avoid cell death and continue to proliferate.